Various controlled release multilayer tablet are available.
For example, with the Geomatrix™ technology customized levels of controlled release of specific drugs and/or simultaneous release of two different drugs and different rates can be achieved from a single tablet. The controlled release is achieved by constructing a multilayer tablet. The combination of layers, each with different rates of swelling, gelling and erosion, is responsible for the rate of drug release within the body. A disadvantage with this technology, however, lies in partial coating/barrier layer(s) as this results in an area with altering drug release as the matrix erodes. For example, a multilayer tablet can transform to a single matrix exposed on all sides to the gastrointestinal fluids upon detachment of the partial coating/barrier layer. This effect is more pronounced when these tablets are taken with food. In some cases the extent of absorption is 50% lower under fasting conditions when compared to fed conditions.
U.S. Pat. No. 4,839,177 discloses a Geomatrix® system for controlled-rate release of active substances with a deposit core of a defined geometric form comprising a polymeric material having a high degree of swelling and a gellable polymeric material, and a support platform consisting of a polymeric material insoluble in aqueous fluids applied to the deposit core such that it partially coats the deposit core. Although the system provides a uniform rate of release, a disadvantage is that the rigid support platform can crack or flake before the active substance is completely released.
U.S. Pat. Nos. 5,422,123, 5,780,057 and 6,294,200 describe improvements wherein the support platform is made of polymer substances which are slowly soluble and/or gellable in aqueous fluids, and plasticizers, such that the support platform does not crack or flake before the drug is completely released from the deposit core. However, while these patents disclose systems wherein surface area of release is reduced by covering two or more surfaces of the deposit core, in practice such systems are difficult to manufacture at an industrial scale, especially systems wherein two lateral surfaces and one planar surface are coated by the support platform.
Published U.S. Application No. US 2002/0090394 A1 describes a further modified system including a pH-dependent polymer coating, such that the release does not occur in the stomach, but occurs after the system empties from the stomach. However, this system also has disadvantages in that partial coating/barrier layer(s) below the pH-dependent polymer coating cannot be easily applied on a manufacturing scale, if at least three of the four tablet surfaces are to be coated to provide assured zero-order or uniform release. The partial coating/barrier layer(s) may be applied according to published U.S. Application No. only on one surface. This again results in the area not remaining constant if the matrix erodes. It has also been observed that the partial coating/barrier layer can detach itself from the deposit core upon handling and transport.
U.S. Pat. No. 5,650,169 discloses a pharmaceutical tablet capable of releasing the active ingredients contained therein at subsequent times, the tablet being prepared by a process wherein a three-layered tablet core comprising a first drug-containing layer, an intermediate barrier layer and a third drug-containing layer are covered with an impermeable polymeric film. The first layer presents a raised top, which is removed by abrasion so as to allow contact of the abraded first layer surface with the environment. The composition of the barrier layer is designed to modulate release from the third layer of the tablet. A disadvantage of this system is that it requires removal of the raised top layer by abrasion to provide a means for release of the components of the system. This may not be feasible at an industrial scale. Further, if the abrasion is not uniform, the release of the active ingredients will be affected.
U.S. Pat. Nos. 6,720,005 and 6,733,784 disclose coated, platform-generating tablets. The tablet hydrates and expands upon swallowing such that the membrane covering the coating ruptures mostly around the belly-band surface of the tablet due to swelling of the core, thereby exposing the belly surface of the core tablet to hydrating and eroding liquids. A disadvantage of the system is that the coating is not reliably removed from the belly-band surface always but may rupture at a different weak point. Thus, the surface area of exposure may vary. Also, the system shows a lag time of release of half an hour or more. Many shapes of the core have been suggested in the invention but some of these may accentuate the problems encountered during tablet manufacture. Further, the belly-band surface, which is exposed after the coating ruptures, has the least surface area and other more preferred surfaces are not exposed.
U.S. Pat. No. 6,899,896 discloses a controlled release formulation for setraline having a core comprising a setraline containing composition and a water swellable composition, wherein the water swellable composition is in a separate region within the core. The core is coated with a water-permeable, water-soluble coating having at least one delivery port for release of the drug from the core through the delivery port in the coating.
U.S. Pat. No. 6,706,283 also discloses a controlled release formulation for low solubility drugs which is coated with a non-dissolving, non-eroding coating that controls the influx of water to the core to cause extrusion of a portion of the core through one or more delivery ports.
U.S. Pat. No. 6,770,297 discloses a controlled release delivery system for a solid dosage form with a plurality of controls on the release of a drug which may be initiated at different times.